Some 140 million persons live permanently at high altitudes (>2500 m) in North, Central and South America, East Africa, and Asia. Reviewed here are recent studies which address the question as to whether genetic adaptation to high altitude has occurred. Common to these studies are the use of the oxygen transport system and the passage of time as organizing principles, and the recognition of the multifaceted ways in which genetic factors can influence physiological processes. They differ in terms of study approach and sources of evidence for judging duration of high altitude residence. Migrant, family set, and admixture study designs have been used for comparisons within populations. These collectively demonstrate the existence of genetic influences on physiological characteristics of oxygen transport. Differences in oxygen transport-related traits between Tibetan, Andean and European populations have been interpreted as having demonstrated the existence of genetic influences on high altitude adaptation but there is not consensus as to which groups are the best-adapted. Part of the controversy lies in the kinds of evidence used to assess duration of high altitude habitation. More other information is needed for a fuller appreciation of duration of residence and also features of population history (genetic drift, gene flow) but existing data are consistent with Tibetans having lived at high altitude longer than the other groups studied. Another issue surrounds usage of the term "adaptation." The definition should be based on evolutionary biology and physiological traits linked to indices of differential fertility and/or mortality. Two examples are developed to illustrate such linkages; intrauterine growth restriction (IUGR) at high altitude and the prevalence of Chronic Mountain Sickness (CMS). Interpopulational as well as intrapopulational variation exists in these conditions which appear linked to characteristics of oxygen transport. Both adversely influence survival and appear to be less severe (IUGR) or less common (CMS) among Tibetans than other groups. Thus available evidence suggest that Tibetans are better adapted. Needed, however, are studies which are better controlled for population ancestry, especially in South America, to determine the extent to which Tibetans differ from Andean highlanders. More precise information is also needed regarding the genetic factors underlying characteristics of oxygen transport. Such studies in Tibetan, Andean and Europeans as well as other high altitude populations offers a promising avenue for clarifying the adaptive value of physiological components of oxygen transport and the extent to which such factors differ among high altitude populations.